Targeting T ₁ and T ₂ dual modality enhanced magnetic resonance imaging of tumor vascular endothelial cells based on peptides-conjugated manganese ferrite nanomicelles

Abstract

Tumor angiogenesis plays very important roles for tumorigenesis, tumor development, metastasis, and prognosis. Targeting T ₁/T ₂ dual modality magnetic resonance (MR) imaging of the tumor vascular endothelial cells (TVECs) with MR molecular probes can greatly improve diagnostic sensitivity and specificity, as well as helping to make an early diagnosis of tumor at the preclinical stage. In this study, a new T ₁ and T ₂ dual modality nanoprobe was successfully fabricated. The prepared nanoprobe comprise peptides CL 1555, poly(ε-caprolactone)-block-poly(ethylene glycol) amphiphilic copolymer shell, and dozens of manganese ferrite (MnFe ₂O ₄) nanoparticle core. The results showed that the hydrophobic MnFe ₂O ₄ nanoparticles were of uniform spheroidal appearance and narrow size distribution. Due to the self-assembled nanomicelles structure, the prepared probes were of high relaxivity of 281.7 mM ⁻¹ s ⁻¹, which was much higher than that of MnFe ₂O ₄ nanoparticles (67.5 mM 1 s ⁻¹). After being grafted with the targeted CD105 peptide CL 1555, the nanomicelles can combine TVECs specifically and make the labeled TVECs dark in T ₂-weighted MR imaging. With the passage on, the Mn ²⁺ ions were released from MnFe ₂O ₄ and the size decreased gradually, making the signal intensity of the second and third passage of labeled TVECs increased in T ₁-weighted MR imaging. Our results demonstrate that CL-poly(ethylene glycol)-MnFe ₂O ₄ can conjugate TVECs and induce dark and bright contrast in MR imaging, and act as a novel molecular probe for T ₁- and T ₂-enhanced MR imaging of tumor angiogenesis.